3 research outputs found
Inferring Latent States and Refining Force Estimates via Hierarchical Dirichlet Process Modeling in Single Particle Tracking Experiments
Optical microscopy provides rich spatio-temporal information characterizing
in vivo molecular motion. However, effective forces and other parameters used
to summarize molecular motion change over time in live cells due to latent
state changes, e.g., changes induced by dynamic micro-environments,
photobleaching, and other heterogeneity inherent in biological processes. This
study focuses on techniques for analyzing Single Particle Tracking (SPT) data
experiencing abrupt state changes. We demonstrate the approach on GFP tagged
chromatids experiencing metaphase in yeast cells and probe the effective forces
resulting from dynamic interactions that reflect the sum of a number of
physical phenomena. State changes are induced by factors such as microtubule
dynamics exerting force through the centromere, thermal polymer fluctuations,
etc. Simulations are used to demonstrate the relevance of the approach in more
general SPT data analyses. Refined force estimates are obtained by adopting and
modifying a nonparametric Bayesian modeling technique, the Hierarchical
Dirichlet Process Switching Linear Dynamical System (HDP-SLDS), for SPT
applications. The HDP-SLDS method shows promise in systematically identifying
dynamical regime changes induced by unobserved state changes when the number of
underlying states is unknown in advance (a common problem in SPT applications).
We expand on the relevance of the HDP-SLDS approach, review the relevant
background of Hierarchical Dirichlet Processes, show how to map discrete time
HDP-SLDS models to classic SPT models, and discuss limitations of the approach.
In addition, we demonstrate new computational techniques for tuning
hyperparameters and for checking the statistical consistency of model
assumptions directly against individual experimental trajectories; the
techniques circumvent the need for "ground-truth" and subjective information.Comment: 25 pages, 6 figures. Differs only typographically from PLoS One
publication available freely as an open-access article at
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.013763
Remark on algorithm 705: A Fortran-77 software package for solving the Sylvester matrix equation AXBT + CXDT = E
We present a number of corrections to Algorithm 70